Pteridines, hydration

The results of the calculations showed that the methodology could accurately predict the difference between purine and pteridine hydration... 

Hjdroxy-3,4-dihydro-pteridin4 1,0 g (6 mMol) 2-Hydroxy-pteridin-Hydrat in 100 ml 0,1 n Natronlauge wird bei 2071 bar iiber 0,5 g Palladium/Kohle (10%) bis zur Beendigung der Wasserstoff-Aufnahme (—20 Min.) hydriert. Das Filtrat wird auf pH 6 gebracht, der erhaltene Niederschlag wird abgesaugt und aus Wasser umkristallisiert Ausbeute 67% d.Th. die Kristalle farben sich bei 250° dunkel, ohne zu schmelzen. 

The spectra of protonated polyaza heterocycles are frequently complicated by the occurrence of covalent hydration. This is more common with polycyclic systems, e.g. pteridine. 

Studies on covalent hydration of N-heterocycles (67AG(E)919,76AHC(20)117) have revealed the diagnostic value of alkyl substituents in structural assignments due to their steric hindrance effects in addition reactions. C-Methyl substituents are therefore also considered as molecular probes to solve fine-structural problems in the pteridine field. The derivatives... 

Considering the four potential monohydroxypteridines, pteridin-4- and -7-one 56JCS3443) behave normally whereas pteridin-2- and -6-one (25) form covalent hydrates. The reversible hydration of nitrogen heterocycles was actually discovered with pteridin-6-one (52JCS1620),... 

The molecular features of covalent hydration are also present in the dihydroxy series, i.e., in pteridine-2,6-dione (30) and in pteridine-4,6-dione. The latter compound is hydrated only at the C(7)—N(8) double bond, whereas (30) forms two hydrated species, 7-hydroxy-7,8-dihydro- (29) and 4-hydroxy-3,4-dihydro-pteridin-2,6-dione (31) (equation 8). Structure (29) is thermodynamically the more stable substance (31) is formed more rapidly in solution but disappears slowly with time (63JCS5151). Insertion of a 4-methyl group greatly reduces the extent of 3,4- in favour of 7,8-hydration by a blocking effect . 

With pteridine (1) the covalent hydration is a complex matter since the general acid-base catalyzed reaction provides a good example of a kinetically controlled addition to the... 

A novel type of ring closure is the reaction of 6-amino-5-dichloroacetylaminopyrimidines (285) with sulfur and morpholine under the conditions of a Kindler reaction (B-64MI21605). 7-Morpholinopteridin-6-ones (287) are formed, either via thiooxamide derivatives (286) or via corresponding 7,8-dihydropteridines (284 equation 102). Chloral hydrate also reacts with 2-substituted 5,6-diaminopyrimidin-4-ones to form pteridin-6-ones (56JCS3311, 64JCS565) by a so far unknown mechanism. 

Pteridine [91-18-9] M 132.2, m 139.5-140°, pKj 4.05 (equilibrium, hydrate), pK 11,90 (OH of hydrate). Crystd from EtOH, benzene, n-hexane, n-heptane or pet ether. It sublimes at 120-130°/20mm. Stored at 0°, in the dark turns green in the presence of light and on long standing in the dark. 

Xanthopterin monohydrate (2-amino-4,6-dihydroxypteridine, 2-amino-pteridin-4,6(lff,5ff)-dione) [5979-01-1 (H2O), 119-48-8 (anhydr)] M 197.2, m <300", pK, 1.6 (basic), pKj 6.59 (acidic), PK3 9.31 (acidic)(anhydrous species), and pKj 1.6 (basic), pK2 8.65 (acidic), PK3 9.99 (acidic)(7,8-hydrated species). Purification as for isoxanthopterin. Crystd by acidifying an ammoniacal soln, and collecting by centrifugation followed by washing with EtOH, ether and drying at 100° in vacuo. Paper chromatography Rp 0.15 ( -PrOH, 1% aq NH3, 2 1), 0.36 ( -BuOH,AcOH, H2O, 4 1 1) and 0.47 (3% aq NH3). [Inoue and Perrin J Chem Soc 260 7962 Inoue Tetrahedron 20 243 I964 see also Blakley Biochemistry of Folic Acid and Related Pteridines North Holland Publ Co, Amsterdam 1969.]... 

Pteridin-6-one (179) is probably hydrated in aqueous solution and, therefore, best represented by structure Ultraviolet spectral... 

The physical properties of the pyridopyrimidines closely resemble those of their nearest A-heteroeyclie neighbors the quinazolines and the pteridines. Thus, in common with the pteridines, the presence of groups capable of hydrogen-bonding markedly raises the melting point and lowers the solubility. - The acid dissociation constants (pif a values) and ultraviolet absorption spectra of all four parent pyridopyrimidines have been determined by Armarego in a comprehensive study of covalent hydration in these heterocyclic systems. The importance of these techniques in the study of covalent hydration, and... 

No comparable study of the hydration of the C=N bond has been made although its properties lie between those of the C=C and C=0 bonds. The hydration of SchifiFbases, such as benzylideneaniline (1), to cations of Dimroth bases, such as 2, is well-known, but attempts to follow this reaction kinetically have been frustrated by the ready breakdown of the neutral species, e.g. 2, to benzaldehyde and aniline. About ten years ago, workers in this Department were surprised to find the C=N bond in many pteridines is capable of hydration, analogous to the reaction 1 f 2. The surprise stemmed principally... 

Following these discoveries, we have made an extensive exj)eri-mental study of covalent hydration and find it is very common, not only in the pteridine series but also in several simpler families of poly-azanaphthalenes. The methods used to diagnose this phenomenon, its... 

Heterocyclic compounds that have water bound covalently across a C=N bond behave as secondary alcohols. When subjected to very gentle oxidative conditions, they are converted into the corresponding 0x0 compounds. Potassium permanganate in 0. IN sodium hydroxide at room temperature has been used to oxidize 2- and 6-hydroxypteri-dine to 2,4- and 6,7-dihydroxypteridine, respectively. In contrast, 4-hydroxypteridine was not attacked by this reagent even at 100°. Hydrogen peroxide in acid solution was used to oxidize quinazoline quinazoline 3-oxide 1,3,5-, 1,3,7-, and 1,3,8-triazanaphthalene and pteridine (which hydrate across the 3,4-double bond in the... 

As is pointed out in the introduction to Section II, the presence or absence of water in the solid state gives no indication as to whether or not covalent hydration occurs in aqueous solution. However, many examples are known of substances which hydrate strongly in solution and also in the solid state. Thus, 2-hydroxy- and 6-hydroxy-pteridine crystallize with one molecule of water. On heating, the former loses water rapidly only at 180°, whereas the latter retains all of the water up to 180° where it begins to darken. ... 

Covalent hydration has been demonstrated in the following families of compounds 1,6-naphthyridines, quinazolines, quinazoline. 3-oxides, four families of l,3,x-triazanapththalenes, both l,4,x-triazanaphthalenes, pteridines and some other tetraazanaphthalenes, and 8-azapurines these compounds are discussed in that order. In general, for any particular compound (e.g. 6-hydroxypteridine) the highest ratio of the hydrated to the anhydrous species follows the order cation > neutral species > anion. In some cases, however, anion formation is possible only when the species are hydrated, e.g. pteridine cf. 21 and N-methyl-hydroxypteridines (Section III, E, 1, d). Table V in ref. 10 should be consulted for the extent of hydration in the substances discussed here. 

Of all the heteroaromatic compounds that have been examined qualitatively and quantitatively for covalent hydration, the pteridines constitute the largest series. Most of the quantitative relationships which were used in earlier discussions were first derived for the hydroxypteridines. Also most of the known examples of hydration in anions were found in this series. 

The blocking effect of the methyl group in 4-methylpteridine has been found to decrease the ratio of the hydrated to the anhydrous species in the neutral molecule and in the cation,but the small proportion of hydrated cation rapidly undergoes the ring-opening reaction 19 20 and hence is steadily regenerated from its anhydrous form. 2-Methylpteridine behaves like pteridine, but in 7-methyl-pteridine the action at a distance (+M) effect of the methyl group (see Section III,C,2) produced a smaller ratio of the hydrated to anhydrous species. 

In strong alkaline solution pteridine behaves as a weak acid with a piCa value of 11.21. To explain this property, the resonance-stabilized anion 21 was derived from the hydrate 16. 

Most of the work done in the pteridine series has been concerned with the equilibria between the neutral species and the anions. This work was more fruitful than that involving the cations because all three of the values, p /, p a , and pK/ (for definitions, see Section II, A), could be determined, and, from these, ratios of the hydrated to the anhydrous forms were calculated. Furthermore, the kinetics in the... 

The ratio, at equilibrium, of the hydrated to anhydrous forms (for both neutral species and anions) has been measured for the following 2-hydroxjrpteridine and its 4-, 6-, and 7-methyl and 6,7-dimethyl derivatives 6-hydroxypteridine and its 2-, 4-, and 7-methyl derivatives 2,6-dihydroxypteridine and 2-amino-4,6-dihydroxypteridine. The following showed no evidence of hydration 4- and 7-hydroxy-pteridine 2,4-, 2,7-, 4,7-, and 6,7-dihydroxypteridine and 2-amino-4-hydroxypteridine. The kinetics of the reversible hydration of 2-hydroxypteridine and its C-methyl derivatives (also 2-mercapto-pteridine) have been measured in the pH region 4-12, and all these reactions were found to be acid-base cataljrzed. The amount of the hydrated form in the anions is always smaller than in the neutral species, but it is not always negligible. Thus, the percentages in 2-hydroxy-, 2-hydroxy-6-methyl-, 2-mercapto-, and 2,6-dihydroxypteridine are 12, 9, 19, and 36%, respectively (see also Table VI in ref. 10). 

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